PHILADELPHIA—It's been just a few weeks since Novartis' Entresto flopped a crucial heart failure study in what the drugmaker called a "narrow miss." Now, subanalyses from multiple studies show Entresto had a "profound effect" on some patients, giving Novartis hope for a second go.
Heart failure patients with an ejection fraction below 57% showed a stronger clinical response on Entresto than patients with ejection fractions above that threshold, according to a combined late-breaking subanalysis from the Paragon-HF and Paradigm-HF trials presented Saturday at the American Heart Association Scientific Sessions.
Dave Soergel, Novartis’ global head of cardiovascular, renal and metabolic drug development, said those data in reducing cardiovascular events in patients with a lower ejection fraction range helped Novartis learn more about Entresto's efficacy––and its chances in future heart failure trials.
"This gives us more confidence that what we see in the effect of Entresto is real," Soergel said.
Heart failure ejection fractions below 40% are usually defined as "reduced"––an indication in which Entresto is already approved to reduce the risk of CV death and hospitalizations––while fractions above 40% are defined as "preserved," an indication which currently has no approved treatment.
Novartis also presented a separate subanalysis from the Paragon-HF trial showing female heart failure patients with a preserved ejection (HFpEF) fraction showed a stronger clinical response to Entresto than male patients. While Soergel said other heart failure studies had shown a similar sex difference in treating ejection fractions, Novartis was still "surprised" by the data and didn't have an explanation for the difference.
"If there hadn’t been other studies that had shown it before, we probably wouldn’t have had much of a basis for building on that," Soergel said. "It suggests there might be something underneath it, but we don’t understand what that is right now."
The newest subanalyses could help Novartis build a case for Entresto in heart failure after Paragon-HF missed its primary endpoint in July with a statistically insignificant 13% reduction in heart failure hospitalizations and cardiovascular death over valsartan.
Entresto sought to become the first drug approved to treat HFpEF, which affects an estimated 13 million patients globally. Soergel said the drugmaker would present its data to global health authorities to determine the next step in the indication. That flop imperiled Novartis' high hopes for Entresto, which included $5 billion in peak sales in some analysts' estimations.
In September, Novartis pointed to subgroups in the Paragon-HF trial to make its case for Entresto's narrow miss, saying patients with a left ventricular ejection fraction equal to or below the median of 57% saw a 22% reduction in total CV events, and female patients showed a 27.5% reduction in the same measure.
In other data presented in Philadelphia, three other Entresto studies––Pioneer, Evaluate and Prove––showed Entresto was well tolerated in patients who were hospitalized or nearer to a hospitalization and that the drug lowered a key biomarker in patients at risk of cardiac strain.
Soergel said the newest data breakdown would help bolster Entresto's chances.
"All of this reinforces the fact that we’re in heart failure to stay and we’re proud of the legacy we’ve built," he said.